Tissue bonding insect repellent

ABSTRACT

The present disclosure generally provides topically applicable insect repelling compositions, and in some embodiments, topically applicable insect repelling and UV protecting compositions. The compositions comprise a polymerization product of a polyol, a diisocyanate and at least one insect-repelling compound. The resulting polymers advantageously bond superficially to skin or hair, thereby localizing repellents and preventing systemic absorption. While not being bound by theory, it is believed that the localization of repellents to the surface of the skin renders them safer, wherein such repellents are not vaporized and do not have a disagreeable odor. The repellents advantageously interact with tactile insect activity, thereby preventing parasitic activity, such as drawing blood or the communication of pathogens.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims benefit of the U.S. Provisional Application No.62/659,096, filed on Apr. 17, 2018, which is hereby incorporated byreference in its entirety.

TECHNICAL FIELD

The present disclosure generally provides topically applicable insectrepelling compositions, and in some embodiments, topically applicableinsect repelling and UV protecting compositions. The compositionscomprise a polymerization product of a polyol, a diisocyanate and atleast one insect-repelling compound. The resulting polymersadvantageously bond superficially to skin or hair, thereby localizingrepellents and preventing systemic absorption. While not being bound bytheory, it is believed that the localization of repellents to thesurface of the skin renders them safer, wherein such repellents are notvaporized and do not have a disagreeable odor. The repellentsadvantageously interact with tactile insect activity, thereby preventingparasitic activity, such as drawing blood or the communication ofpathogens.

BACKGROUND OF THE INVENTION

The present invention relates generally to insect-repelling compositionsfor topical application to skin and hair. Bites of mosquitoes belongingto the genera Anopheles Meigen, Aedes Meigen, Culex L. and Haemagogus L.are a general nuisance and are responsible for the transmission ofpernicious tropical diseases, such as malaria, hemorrhagic dengue andyellow fevers and filariasis (elephantiasis). Plants are natural sourcesof mosquito repelling essential oils (EOs), glyceridic oils andrepellent and synergistic chemicals. Plants that have insect repellingEOs include citronella [Cymbopogon nardus (L.) Rendle, C. winterianusJowitt ex Bor], eucalyptus (Eucalyptus L'Her. spp.), camphor [Cinnamomumcamphora (L.) J. Presl], cinnamon (Cinnamomum zeylanicum Blume), clove[Syzygium aromaticum (L.) Men. & L. M. Perry], geranium (Pelargoniumgraveolens L'Her.), lavender (Lavandula angustifolia Mill.), lemon[Citrus x limon (L.) Osbeck], lemongrass [Cymbopogon citratus (DC.)Stapf], peppermint (Mentha x piperita L.). Repellent chemicals presentin EO compositions or added as pure natural ingredients includegeraniol, limonene, p-menthane-3,8-diol, nepetalactone and vanillin.Essential oils have also been used in combination with synthetic insectcontrol agents having mosquito repellent properties such as pyrethroids,N,N-diethyl-m-toluamide (DEET), (±)-p-menthane-3,8-diol (PMD) anddialkyl phthalates. Scientific literature sources provide evidence forthe mosquito repellency of many of the EOs and individual chemicalcomponents found in EOs.

Many insects, in addition to mosquitos, are classified as pests, andmany efforts have been made to eradicate or at least control them.However, although effective poisons have been produced, various insectshave developed resistance to them and others have been able to detectand avoid poisons. Furthermore, many poisons have undesirable effects onhuman and other animal life, and therefore uses thereof have often beenregulated or forbidden. In many cases, an effective repellent ispreferred to poisons. Similarly, when such repellents are of lowtoxicity they may be applied to the human body and onto pets, zooanimals and livestock. Some repellents are foul smelling anddiscoloring, these adverse properties can seriously limit theirutilities. Many of the useful insect repellents reported in theliterature are-tertiary amides and of these the one heretofore regardedas the most effective all-purpose insect repellent isN,N-diethyl-m-toluamide (DEET).

Desirably, such compounds also would be of improved physicalcharacteristics, such as of even better aroma, non-staining character,even lower toxicity, improved stability, greater substantivity tosubstrates, and repellency against a broader group of insect types.

In many instances it is more advantageous to repel insect pests from agiven place than it is to kill them after they have entered it. Someinsect pests inherently are difficult to kill, or the nature of theplace where the pests are found may make it undesirable to kill themthere. It is considered to be more desirable to repel pests such asmosquitoes and flies from the vicinity of an animal. In a number ofinstances, such as in the treatment of laborers in the field, it isdesirable to use repellents to prevent the movement of insect pests intoan area and from one area to another.

Pyrethrins are a class of compounds from blossoms of pyrethrum flowers(Chrysanthemum cinerariaefolium) grown mainly in East Africa, containinga cyclopropanecarboxylate group. The pyrethrins are effective as insectrepellents, but they are short-lived. The cyclopropanecarboxylate can bemodified by hydrolyzation of the ester group to be useful in the presentinvention.

Although pyrethrins display relatively low toxicity toward mammals anddo not leave harmful residues, they undergo rapid biodegradation, theyhave poor photooxidative stability, their availability is uncertain, andit is costly to extract and process them. Thus, their use has beenlimited. For a number of years, efforts have been underway around theworld to produce synthetic cyclopropanecarboxylate insecticides,pyrethroids, which would overcome these disadvantages. 5-Benzyl-3-furylmethyl chrysanthemate (resmethrin), a powerful contact insecticide, wasan early success. A notable recent result of these efforts was thediscovery of the pyrethroid, 3-phenoxybenzyl3-(β-β-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate, having theknockdown attributes of the natural pyrethrins and resmethrin togetherwith a previously unattained level of photooxidative stability.

Lemon eucalyptus oil is said to be as effective as DEET (N,N-diethyl-m-toluamide) in insect repellents, and is believed to berecommended by the Center for Disease Control (CDC) and the EPA for useagainst the mosquitoes known to carry West Nile virus, which causes WestNile fever. Oil of lemon eucalyptus is reddish in color and is said tohave a menthol-like smell and a coolant like effect. It is apparentlyused in aromatherapy for relief of congestion, emphysema, and smokers'cough, as Well as for sore throats. It is said to be an antifungal andanti-infectious agent suitable for helping against respiratory and skininfections, and to have anti-inflammatory and insecticidal properties.It can apparently be applied by inhalation, bath, lotion, ointment,diffuser, or a room spray. According to contraindications, lemoneucalyptus oil should be diluted prior to applying it on the skin.

Examples of patents relating to insect repellents include U.S. Pat. No.4,756,905, entitled “INSECT-REPELLENT CAMOUFLAGE COMPOSITION”, issued onJul. 12, 1988 to J. Melnik discloses a composition for repelling insectsand camouflaging the human skin. The insect repellent, N,NDiethyl-m-toluamide (“DEET), and a camouflage pigment are combined alongwith an optional emulsifier to allow a single application to serve boththe camouflage and insect repellent functions.

U.S. Pat. No. 3,590,118, entitled “LONG LASTING INSECT REPELLENT FILMSFOR SKIN AND OTHER SUBSTRATES”, issued on Jun. 29, 1971 to J. A.Conrady, et al. discloses a long-lasting insect repellent film for skinapplication. The active chemical agents are dissolved in interpolymerresins to provide a slow release system for the active chemical agentswhen spread and dried as a film on a human being. The coating can beapplied by spraying or spreading and it is alleged to be easilyremovable with a soapy water solution.

U.S. Pat. No. 2,435,005, entitled “SKIN PROTECTIVE OINTMENT”, issued onJan. 27, 1948 to W. F. Huppke, et al. discloses a cream or ointmentcontaining a film-former So that the cream or ointment forms a film onthe wearer's skin. The cream or ointment may include an insect repellentor a sunscreen, or both. Preferably, the film former is a mixture ofethyl cellulose and shellac.

U.S. Pat. No. 4,477,467, entitled “INSECT REPELLENT”, issued on Oct. 16,1984 to K. Nishizawa, et al. discloses the use of DEET in combinationwith certain proton acceptors for the purpose of inhibiting theabsorption of DEET into the wearer's skin.

U.S. Pat. No. 2,356,801, entitled “INSECT REPELLENT COMPOSITION”, issuedon Aug. 29, 1994 to B. V. Travis, et al. discloses an insect repellentcomposition in which four insect repellent compounds are combined toimprove the effectiveness of the composition.

Nevertheless, there is a need for insect repelling compositions that arelong lasting, non-irritating and resist absorption by the skin. Thepresent disclosure addresses these needs. Further, there is a need for acomposition that provides both insect repelling and sun-blocking effectsfor a prolonged period of time, even in the presence of water.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to insect repellents that are chemicallybonded to a multi-armed molecule, with at least one arm capable ofbonding superficially to skin. The backbone molecule is apoly(ethylene), or poly(propylene) or poly(ethylene)-poly(propylene)copolymer with end groups comprising amine or isocyanate groups. Thatis, when these multifunctional molecules are reacted with known insectrepellent a molecule results that contains these repellents and alsoretains a skin bonding moiety. For example, a polyalkane with a terminalisocyanate or amine group will readily bond to superficial skin, that isdead skin, and whatever is attached to the molecule is sequestered frompermeation into tissue, thereby preventing an immunological response.Furthermore, such a skin localized insect repellent will not have anoticeable odor, but will repel insects based on their landing contact.

Basic starting molecules of the present invention comprise polyalkenesterminated with amines or isocyanate groups. These groups react with thependent groups of any insect repellents containing amine or hydroxylgroups. Insect repellents not containing these groups usually can bemodified to produce a terminal amine or hydroxyl group without losingthe insect repellent effectiveness. For example, esters can be convertedto alcohols.

For example, an alcohol such as Geraniol is found in roses (with2-phenylethanol), citronella oil, pomerosa oil, geraniums, and otherflowers. A-Terpineol is found in pine oil and juniper; it is used as aperfume and bactericide in many household cleaners. Menthol is found inpeppermint and other mint oils. It has a pleasant cooling taste, sinceit causes the “cold” receptors on the tongue to activate at highertemperatures than normal (such as body temperature). Menthol is used incough drops, shaving lotion, and mentholated tobacco. In particular,Citronellol, or hydro geraniol, is a natural acyclic monoterpenoid. Bothenantiomers occur in nature. (+)-Citronellol, which is found incitronella oils, including Cymbopogon nardus (50%), is the more commonisomer. (−)-Citronellol is found in the oils of rose (18-55%) andPelargonium geraniums. Or alternatively Eucalyptol, or Azadirachtin, achemical compound belonging to the limonoid group, is a secondarymetabolite present in neem seeds. It is a highly oxidizedtetranortriterpenoid which boasts a plethora of oxygen-bearingfunctional groups, including an enol ether, acetal, hemiacetal,tetra-substituted epoxide and a variety of carboxylic esters.

Synthetic repellents useful in the present compositions include phthalicacid dimethyl ester, 1.2-ethyl hexane 1,3-diol,3,4-dihydro-2,2-dimethyl-4-oxo-2H-pyran-6-carboxylic acid-n-butyl ester,succinic acid dipropyl ester, N,N-diethyl-3-methyl-benzoic acid amideand pyridine-2,5-dicarboxylic acid-d-n-propyl ester, all of which areuseful in the present invention. In some embodiments, molecules of thepresent invention comprising neoalkanamide groups, which are effectivein repelling insects other than mosquitos, such as arachnids, blackflies, carpenter ants and deer ticks. In view of the relatively smallnumber of useful insect repellents known, efforts continue to be made todiscover additional repellents which would be of greater repellentactions and of longer lasting effects.

Natural insect repellents are obtained from plants by extracting theoils by means of cold expeller pressing, rolling or centrifugation, forexample, the essential ingredients are also extracted from the vegetablematter, yielding an oil with superior insect repellent properties. Forexample, some of the essential ingredients found in Neem oil are variousfractions of limonoids, terpenes and terpenoids such as nimbin,salannin, and nimbiol, present in the Azadirachta lndica (Neem) tree andits leaves, bark and seeds. Some of the insect repellent chemicals,which are more numerous in the crude cold pressed oil than in therefined oil, are meliantriol, nimbinin, nimbidin, nimbidol, thionimone,nimatone, nimidol, nimbedic acid, nimbedinic acid, neonimbidin,nimidinin, gedunim, vapinin, meldenin, and vilasinin, as well as certainphyto sterols like beta sitosterol, kaempferol, and some flavonoids suchas quercetin and myricetin. Further, Azadirachtin has numerous homologsremaining in the crude pressed oil that do not seem to carry over aswell when solvent extracted or heated. They are Azadirone, Azadiradione,beta hydroxy Azadiradione, and delta epi Azadiradione.

By themselves, these bio-chemicals may not have the same bio-activity orinsecticidal properties as Azadirachtin, but together they show superioreffectiveness as insect repellents. The effectiveness can be furtherimproved by combining the bio-chemicals with other crude cold expellerpressed or ultra-centrifuged essential oils and ingredients that alsopossess insect repellent properties. In particular, it is most effectiveto combine Neem oil with Citronella oil and Lemon Eucalyptus oilprocessed in the same manner. The crude cold expeller pressed oil ofCitronella contains citral, citronellal, limonene, geraniol, linalool,dipentene and pentinoids. The unrefined oils can be reacted with thebase molecule of the present invention, or preferably with purifiedcomponents of these natural oils.

Other ingredients may be placed on the base molecule to make a proteinbonding insect repellent molecule or combined with the protein bondinginsect repellent in a mixture to increase the efficacy of the essentialoil based molecules. These include thymol or oil of thyme, peppermintoil, menthol, camphor, garlic oil (allyl sulfide), Wintergreen oil(methyl salicylate), oil of pennyroyal (pulegone), oleoresin capsicum,and other like substances.

However, taken alone, these substances have minimal effect. Further,thymol may be used more as an antioxidant then to increase theeffectiveness of the essential oil composition. UV absorbers orstabilizers may also be added in order to preserve these cold pressedoils against the potential harmful effects of sunlight. Further, theaddition of UV absorbers forms a combination sunscreen/insect repellent.Some useful UV absorbers or stabilizers are benzophenones, salicylateesters, cinnamate esters, p-aminobenzoic acid (PABA) esters, and thelike.

The fatty alcohols, fatty acid alkyl esters and fatty acids may beobtained by means of a simple chemical reaction from natural ornature-identical, toxicologically harmless raw materials, e.g. by meansof hydrolysis, reesterification, hydrogenation, high-pressurehydrogenation, hardening and/or dehydration as known in the prior art.The fatty oils used according to the invention may also be obtained bymeans of conventional processes from oil-supplying materials such asplant seeds and animal fats. Accordingly, the insect repellent accordingto the invention contains one or several substances prepared fromcompletely harmless, synthetic (nature-identical) basic substances ordirectly from natural basic substances, and, consequently, has the leasttoxicological and irritative risk with an excellent repelling effect. Itis preferably used by applying it onto the skin or hair of man and beastto repel flying, biting and sucking insects.

Definitions

The following terms are used herein.

As used herein, the term “synthetic insect repellent” includes withoutlimitation Methyl anthranilate and other anthranilate-based insectrepellents, Benzaldehyde, for bees, DEET (N,N-diethyl-m-toluamide),Dimethyl carbate, Dimethyl phthalate, Ethylhexanediol, lcaridin(picaridin), Bayrepel, and KBR 3023, lndalone, a mixture of 60% Dimethylphthalate, 20% lndalone, 20% Ethyl Hexanediol, IR3535(3-[N-Butyl-N-acetyl]-aminopropionic acid, ethyl ester), Metofluthrin,Permethrin, SS220, and Tricyclodecenyl allyl ether.

As used herein, the term “natural insect repellent” includes withoutlimitation Beautyberry (Callicarpa) leaves, Birch tree bark made intotar and combined with another oil (e.g., fish oil) at ½ dilution, BogMyrtle (Myrica Gale), Catnip oil whose active compound is NepetalactoneCitronella oil, Essential oil of the lemon eucalyptus (Corymbiacitriodora) and its active compound p-menthane-3,8-diol (PMD), Neem oil,Lemongrass, Tea tree oil from the leaves of Melaleuca alternifolia, andTobacco.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 shows protein bonding isocyanate groups attached to a triol,forming a tissue bonding molecule of the invention.

FIG. 2 shows a tissue bonding molecule of FIG. 1, whereon one of theisocyanate groups has been bonded to citronellol, an insect repellent,to form a protein bonding insect repellent of the invention.

FIG. 3 shows a protein bonding insect repellent of FIG. 2 with one ofthe protein bonding isocyanate groups bonded to 4-Aminobenzoic acid, asunscreen, to form a protein bonding insect repellent stabilized with asunscreen of the present invention.

FIG. 4 is a graph depicting the percentage of mosquitos not landing andbiting over a 24-hour period of time using compositions of the presentinvention compared with 100% DEET.

DETAILED DESCRIPTION OF THE INVENTION

The present insect repellent composition includes one or more insectrepellent agent bonded to a skin bonding polymer composition, andanhydrous base. The insect repellent composition can include additionalcomponents commonly found in insect repellent compositions including,for example, surfactants, pH adjusting agents, thickeners, emollients,moisturizers, coloring agents, preservatives, antioxidants, chelatingagents, UV absorbers and fragrances.

The compositions of the invention may be in any of the forms which aresuitable for topical application, in particular in the form ofnonaqueous gels, in the form of emulsions obtained by dispersion of afat phase (also termed the oily phase) in a nonaqueous phase or thereverse, or multiple emulsions. They may be more or less fluid and havethe appearance of a white or colored cream, a pomade, a milk, a lotion,a serum, a paste, a powder, a solid stick, and may optionally bepackaged as an aerosol and in the form of a foam or spray. Thesecompositions are prepared using the usual methods.

In a particular embodiment of the invention, the composition is in theform of an emulsion and then comprises at least one oily phase. Theproportion of the oily phase of the emulsion may be from 1% to 80% byweight, preferably 2% to 50% by weight and more preferably 2% to 40% byweight with respect to the total composition weight. The fats in theoily phase, in particular oils, and the emulsifying and co-emulsifyingagents which may be present, used in the composition in the form of anemulsion are selected from those conventionally used in the cosmetics ordermatological field. The emulsifying and co-emulsifying agent, whenpresent, are generally present in a proportion of 0.1% to 30% by weight,preferably 0.3% to 20% by weight and more preferably 0.5% to 15% byweight with respect to the total composition weight. The emulsion mayalso contain lipid vesicles in addition to or in place of theemulsifying and/or co-emulsifying agents.

The emulsions generally contain at least one emulsifying agent selectedfrom amphoteric, anionic, cationic or nonionic emulsifying agents usedalone or as a mixture. The emulsifying agents are suitably selected as afunction of the continuous phase of the emulsion to be produced. Whenthe emulsion is a multiple emulsion, it generally comprises anemulsifying agent in the primary emulsion and an emulsifying agent inthe external phase into which the primary emulsion is introduced.

Emulsifying agents which may be used to prepare emulsions which may becited, are for example alkyl esters or sorbitan ethers, glycerol orsugars; silicone surfactants such as dimethicone copolyols, such as themixture of cyclomethicone and dimethicone copolyol, marketed under thetrademarks DC 5225 C and DC 3225 C by Dow Corning and such asalkyl-dimethicone copolyols such as Lauryl Methicone copolyol marketedunder the trademark “Dow Corning 5200 Formulation Aid” by Dow Corning,Cetyl dimethicone copolyol marketed under the trademark Abil EM 90® byGoldschmidt and the mixture of Polyglyceryl-4 isostearate/Cetyldimethicone copolyol/Hexyl laurate marketed under the trademark Abil WE09® by Goldschmidt. It is also possible to add thereto one or moreco-emulsifying agents which, advantageously, may be selected from thegroup comprising esters of fatty acids with a branched chain and polyol,in particular esters of fatty acid with a branched chain and glyceroland/or sorbitan and, for example, polyglyceryl isostearate, such as theproduct marketed under the trademark lsolan GI 34 by Goldschmidt,sorbitan isostearate, such as the product marketed under the trademarkArlacel 987 by ICI, sorbitan isostearate and glycerol, such as theproduct marketed under the trademark Arlacel 986 by ICI, and mixturesthereof.

Examples of emulsifying agents suitable for the preparation of emulsionswhich may be cited are nonionic emulsifying agents such as esters offatty acids and oxyalkylated polyols (more particularlypolyoxyethylated), for example polyethylene glycol stearates such asPEG-100 stearate, PEG-50 stearate and PEG-40 stearate; esters of fattyacids and oxyalkylated sorbitan comprising 20 to 100 OE, for example,and for example those marketed under the trademark Tween 20 or Tween 60by Uniqema; ethers of oxyalkylated (oxyethylenated and/or oxypropylene)fatty alcohols; esters of sugars, alkoxylated or not, such as sucrosestearate and such as PEG-20 methyl glucose sesquistearate; sorbitanesters such as sorbitan palmitate marketed under the trademark Span 40by Uniqema; esters of a dibasic acid and a fatty alcohol, such asdimyristoyl tartrate; mixtures of these emulsifying agents such as amixture of glyceryl stearate and PEG-100 stearate (CTFA name: GlycerylStearate/PEG-100 Stearate) marketed under the trademark Arlacel 165 byUniqema and under the trademark SIMULSOL 165 by SEPPIC; or the mixtureof dimyristoyl tartrate, cetearyl alcohol, Pareth-7 and PEG-25laureth-25, marketed under the trademark Cosmacol PSE by Sasol (CTFAname: Dimyristoyl tartrate/cetearyl alcohol/12-15 Pareth 7/PPG 25laureth 25); mixtures of fatty alcohols and alkyl glycoside, such as thecetearyl alcohol/cetearyl glucoside mixture, for example thecommercially available product marketed under the trademark MONTANOV 68by SEPPIC.

Co-emulsifying agents may be added to said emulsifying agents, such asfatty alcohols containing 8 to 26 carbon atoms, such as cetyl alcohol,stearyl alcohol and a mixture thereof (cetearyl alcohol),octyldodecanol, 2-butyl octanol, 2-hexyldecanol, 2-undecyl pentadecanolor oleic alcohol, or fatty acids, for example.

Examples of oils which can be used in the compositions of the inventionare hydrocarbon-containing oils of animal origin such asperhydrosqualene (or squalane); hydrocarbon-containing oils of vegetableorigin, such as caprylic/capric acid triglycerides such as thosemarketed by Stearineries Dubois or those marketed under the trademarkMiglyol 810, 812 and 818 by Dynamit Nobel, or oils of vegetable origin,for example sunflower, corn, soya, gourd, grapeseed, sesame, hazelnut,apricot, macadamia nut, arara, coriander, castor, avocado, jojoba oil,shea butter oil; synthesized oils; silicone oils such as volatile ornonvolatile polymethylsiloxanes (PDMS) with a linear or cyclic siliconechain, which are liquid or pasty at ambient temperature; fluorinatedoils such as partially hydrocarbonated and/or silicone oils, such asthose described in JP-A-2-295912; ethers such as dicaprylyl ether (CTFAname: Dicaprylyl ether); and benzoates of C.sub.12-C.sub.15 fattyalcohols (Finsolv TN from FINETEX); arylalkyl benzoate derivatives suchas 2-phenylethyl benzoate (X-Tend 226 from ISP); amide oils such asisopropyl N-lauroyl sarcosinate (ELDEW SL-205 from Ajimoto) and mixturesthereof.

The oily phase may also comprise one or more fats selected, for example,from fatty alcohols (cetyl alcohol, stearyl alcohol, cetearyl alcohol),fatty acids (stearic acid) and waxes (paraffin, polyethylene waxes,carnauba, beeswax).

The compositions of the invention may also contain one or more organicsolvents which may be selected from the group constituted by hydrophilicorganic solvents, lipophilic organic solvents, amphiphilic solvents ormixtures thereof.

Examples of hydrophilic organic solvents which are representative, forexample, are linear or branched monohydric alcohols containing 1 to 8carbon atoms, such as ethanol, propanol, butanol, isopropanol orisobutanol; polyethylene glycols containing 6 to 80 ethylene oxides;polyols such as propylene glycol, isoprene glycol, butylene glycol,glycerol or sorbitol; mono- or di-alkyl isosorbides the alkyl groups ofwhich contain 1 to 5 carbon atoms, such as dimethyl isosorbide; glycolethers such as diethylene glycol mono-methyl or mono-ethyl ether andpropylene glycol ethers such as dipropylene glycol methyl ether.

Amphiphilic organic solvents which are exemplary include polypropyleneglycol (PPG) derivatives, such as esters of polypropylene glycol andfatty acids, PPG and fatty alcohol such as PPG-23 oleyl ether and PPG-36oleate.

Examples of lipophilic organic solvents which are exemplary are fattyesters such as diisopropyl adipate, dioctyl adipate or alkyl benzoates.

The compositions of the present invention may also comprise conventionalcosmetic adjuvants selected from softeners, moisturizers, opacifyingagents, stabilizers, emollients, silicones, anti-foaming agents,fragrances, preservatives, anionic, cationic, nonionic, zwitterionic oramphoteric surfactants, fillers, polymers, propellants, alkalinizing oracidifying agents or any other ingredient which is normally used in thecosmetics and/or dermatological field.

Hydrophilic thickeners which are exemplary include carboxyvinyl polymerssuch as carbopols (carbomers) and Pemulens (Copolymer acrylate/C1O-C30-alkylacrylate); cellulose derivatives such ashydroxyethylcellulose; polysaccharides and in particular, gums such asxanthan gum; and mixtures thereof.

Lipophilic thickeners which are exemplary include modified clays, suchas hectorite and its derivatives, for example products marketed underthe trademark Bentone.

Preservatives which are exemplary include parahydroxybenzoic acid estersalso known as Parabens® (in particular methyl paraben, ethyl paraben,propyl paraben), phenoxyethanol, formol liberators such as, for example,imidazolidinyl urea or diazolidinyl urea, chlorhexidine digluconate,sodium benzoate, caprylyl glycol, iodopropynyl butyl carbamate,pentylene glycol, alkyl trimethylammonium bromide such asmyristyl-trimethylammonium bromide (CTFA name: Myrtrimonium bromide),dodecyl-trimethylammonium bromide, hexadecyl-trimethylammonium bromide,and mixtures thereof such as the mixture marketed under the trademarkCetrimide® by FEF CHEMICALS. The preservative may be present in thecomposition of the invention in an amount of 0.001% to 10% by weightwith respect to the total composition weight, especially 0.1% to 5% byweight, and in particular 0.2% to 3% by weight.

Examples of fillers which may be included in the compositions of theinvention are, for example, pigments; silica powder; talc; polyamideparticles, in particular those marketed under the trademark ORGASOL byAtochem; polyethylene powders; powders of natural organic materials suchas starch powders, in particular of corn, wheat or rice starch, whichmay or may not be cross-linked, such as powders of starch cross-linkedby octenylsuccinate anhydride, marketed under the trademark DRY-FLO byNational Starch; microspheres based on acrylic copolymers, such as thoseformed from an ethylene glycol dimethacrylate/lauryl methacrylatecopolymer marketed by Dow Corning under the trademark POLYTRAP;polymethylmethacrylate powders such as those marketed under thetrademark MICROPEARL M 100 by Matsumoto; expanded powders such as hollowmicrospheres, in particular microspheres marketed under the trademarkEXPANCEL by Kemanord Plast or under the trademark MICROPEARL F 80 ED byMatsumoto; silicone resin microbeads, such as those marketed under thetrademark TOSPEARL by Toshiba Silicone; polyurethane powders, such ashexamethylene diisocyanate/trimethylol hexyllactone copolymer marketedunder the trademark Plastic Powder D-400 by Toshiba Pigment (CTFA name:HD1/Trimethylol Hexyllactone Crosspolymer); and mixtures thereof. Whenthey are present, these fillers may be in quantities of 0.001% to 20% byweight, preferably 0.1% to 10% by weight and more preferably 1% to 5% byweight with respect to the total composition weight.

The compositions of the invention may constitute a skin care products,or a veterinary products.

Skin Bonding Polymer Component

The insect repellent composition includes a skin bonding polymercomponent. The skin bonding polymer component can include any polymerthat, when applied to the skin, helps hold the insect repellent agent tothe skin. The skin bonding polymer component holds the insect repellentagent in proximity to skin tissue when applied to the skin tissue sothat the insect repellent agent can protect the skin tissue from bitinginsects. The skin bonding polymer component can be referred to as thepolymer component. The polymer component can be provided as a polymerhaving an average molecular weight of at least about 2,000. The polymercomponent can be provided as a polymer having an average molecularweight of less than about 500,000.

The present invention also relates to clothing articles and the likethat have the present molecule bonded to them, wherein the coatingsinclude biocompatible polymers based on an aryl group attached to anaromatic ring. More specifically, the present invention relates toclothing articles having coatings, which include multiple insectrepellent groups on one molecule.

Chemical compounds of the present invention comprise aromatic ringstabilized insect repellent moiety. The insect repelling compounds canbe compounds with pendant hydroxyl (OH) or amine (NH) moieties thatreact with pendant isocyanate groups of the polymer to form urethane orurea links, to form a protein bonding molecule containing at least onefree NCO. The polymeric backbone is preferably multifunctional(multi-armed) and capable of concentrating multiple insect repellent andprotein bonding moieties singly or in combination, on a single molecule.Additionally, one or more of the polymeric backbone arms may besubstituted with a protein bonding or clothing article bonding moiety.

In addition to its functional aspects, the polymeric backbone providesshielding benefits to the insect repellent groups, preventing them fromdegradation due to the presence of water. The polymer chain compriseshydrophilic groups and hydrophobic groups. The hydrophilic groups arepositioned such that the overall insect repellent molecule isbiocompatible and does not cause an allergic response which may degradeor otherwise render less functional the insect repellent molecule. Thehydrophobic groups are positioned such that water is repelled from thearomatic ring structure comprising the protein bonding or insectrepellent groups. Clearly, the degree of hydrophobic shielding can beadjusted by the position, size and distribution of hydrophobic andhydrophilic segments on the polymer backbone R1. The interveningaromatic ring structure, positioned between the polymeric backbone R 1and the insect repellent moiety R2, balances the insect repellent orprotein bonding group with an opposing urethane or urea group connectingthe polymeric backbone to the aromatic ring.

Due to the resonant structure of aromatic rings, the effect of theopposing urethane or urea group tends to increase positive charge in thevicinity of the insect repellent functional group, and consequentlytends to increase the stability of such moieties againstphotodegradation and hydrolysis.

The mechanism of this rate retardation may be attributable simply torepulsive electrostatic interactions, which inhibit attack of positivelycharged H ions on the insect repellent functional group and slows therate of its H-catalyzed decomposition.

The invention described herein provides novel insect repellentether-urethane/urea-aromatic-based polymers (“EUA polymers”). Thepolymers of the invention preferably comprise at least two insectrepellent units and contain at least one aromatic ring associated witheach insect repellent unit.

In addition, although less preferred, the present invention can embodyother protective moieties in the insect repellent position, including UVabsorptive compounds containing pendant hydroxyl or amine groups.Alternatively, these EUA-molecules can be used in a cosmetic mode.

Some embodiments of the present invention are coatings for clothingarticles, living area screens, and the like made from one or more of thebonding tissue repellent molecule of the present invention. These insectrepellent articles and coatings made in accordance with the teachings ofthe present invention include embodiments wherein one or more additionalbioactive agent is attached to one of the arms of the polymericbackbone. The bioactive agent can be released at the skin surface orfunction as an interface between the insect repellent and an article ortissue. Preferably, said interface is a covalent bond.

Suitable bioactive agents include, but are not limited to, FKBP12binding compounds such as Zotarolimus, estrogens, chaperone inhibitors,protease inhibitors, protein-tyrosine kinase inhibitors, leptomycin B,peroxisome proliferator-activated receptor gamma ligands (PPARgamma.),hypothemycin, bisphosphonates, epidermal growth factor inhibitors,antibodies, proteasome inhibitors, antibiotics, anti-inflammatories,antisense nucleotides and transforming nucleic acids.

Alternatively, the EUA-based polymers of the present invention may bedelivered as individual molecules with all their functional armsoccupied with one or more insect repellent groups wherein the insectrepellent polymer is eluted from a substrate polymer in a predeterminedfashion. Exemplary embodiments of a delivery device scenario include,but are not limited to, insect-repellent eluting plastics ormonofilaments.

When the isocyanate is attached to an aromatic ring, such as is the caseof the aromatic isocyanates (e.g. toluene diisocyanate), the reactionwith a polyol creates a polyisocyanate. None of the polyisocyanates ofthe present invention are available commercially, and must besynthesized according to embodiments herein given. The object to berecognized is the bonding of aromatic isocyanates tohydrophilic/hydrophobic polyols as herein described create proteinbonding molecules, and in particular, skin and hair bonding molecules.An exemplary three-armed polymer containing three pendant isocyanategroups is depicted in FIG. 1. In this embodiment, the polymer comprisesa polyol, wherein n is independently for each occurrence in an integerranging from 10 to 10,000. In some embodiments, the polyol is apolyethylene oxide, polypropylene oxide or a mixture thereof (i.e., R isindependently for each occurrence H or CH₃).

In an embodiment, the polyisocyanate is modified by reacting one of thependant isocyanate groups with the hydroxyl or amine pendant groups ofan insect repelling compound. For example, as depicted in FIG. 2,citonellol can be reacted with a pendant isocyanate group to form anurethane linkage between the citronellol and the polymer backbone.

The resulting compound may be further modified by reacting one of thependant isocyanate groups with the hydroxyl or amine pendant groups of aUV absorber, thereby producing a compound that has both insect repellingand sun-protecting properties. For example, as depicted in FIG. 3,aminobenzoic acid is reacted with a pendant isocyanate group to form aurethane linkage between the aminobenzoic acid and the polymer backbone.This molecule illustrates a protein bonding pendant NCO, an insectrepellent group of citronellol, and a UV absorptive group ofaminobenzoic acid. These compounds are unusual in having three urethaneor urea linkages between the backbone polymer and the diisocyanate, anda urethane or urea linkages between the protein bonding molecule andinsect repellent and UV absorptive moieties.

More generally, when the diisocyanate is reacted with an alcohol, suchas polyethylene glycol, polypropylene glycol or combinations of theseethers, in sufficient quantities that free NCO groups are pendant, thenthe diisocyanate forms a urethane or urea link (if the glycol isaminated) between the glycol and the aromatic ring of the diisocyanate.The free NCO group can then participate in urea or urethane linkformation when exposed to insect repellent moieties.

The alcohol in this structure is a nucleophile, and bends towardselectronegativity of the oxygen, which is substantially greater thanthat of carbon and hydrogen. Consequently, the covalent bonds of thisfunctional group are polarized so that oxygen is electron rich and bothcarbon and hydrogen are electrophilic, and the insect repellent group ispartially shielded from environmental water.

The aromaticity of the benzene ring between insect repellent moiety andether moiety stabilizes the insect repellent moiety. The aromatic ringis a conjugated ring of unsaturated bonds, lone pairs, or empty orbitalsexhibit a stabilization stronger than would be expected by thestabilization of conjugation alone.

Aromaticity can also be considered a manifestation of cyclicdelocalization and of resonance. This is usually considered to bebecause electrons are free to cycle around circular arrangements ofatoms which are alternately single and double-bonded to one another.These bonds may be seen as a hybrid of a single bond and a double bond,each bond in the ring identical to every other. The model for benzeneconsists of two resonance forms, which corresponds to the double andsingle bonds superimposing to give rise to six one-and-a-half bonds.Benzene is a more stable molecule than would be expected withoutaccounting for charge delocalization.

One skilled in the art will also recognize the theoretical possibilitythat some insect repellent moieties can be sequestered in these polymersby electrostatic interaction with the pi electrons contained in themultiple bonds (i.e., to form clathrate-type or sandwich-likestructures). Indeed, to some extent, these and other possible structuresmay exist in the materials of the present invention.

The diisocyanate depicted in FIGS. 1 to 3 is 2,4-toluene diisocyanate,though other diisocyanates may be used. The incorporation of amulti-armed polymer increases the capacity of a molecule to deliverinsect repellent moieties and contributes to the stability of themolecule. The combination of increased stability and capacity to deliverinsect repellent moieties results in a high insect repellent potency.

A further advantage of these polymers is that they lack the brittlenessof other insect repellent compositions and have sufficient elasticity tocoat and adhere under physiological conditions to clothing articles,such as caps, shirts, or trousers.

The polymers of the present invention can be prepared from polymershaving a multiplicity of nucleophilic groups. Suitable nucleophilicgroups include amines, thiols, hydroxyls, hydroxylamines, hydrazines,amides, guanadines, imines, aromatic rings and nucleophilic carbonatoms.

In particular, the polymer may be a triol of ethylene oxide andpropylene oxide units distributed so as to render the entire polymericbackbone structure biocompatible. For example, the triol may consist ofa copolymer consisting of 25% propylene oxide units and 75% ethyleneoxide units, or their glycols, in a block copolymer structure.

Alternatively, diols of ethylene oxide and propylene oxide or copolymersof these can be grafted to a small trifunctional center Such astrimethylolpropane through urethane links. In some cases an absorbablepolymer backbone is desired. Typical absorbable, biocompatible links areester, polysaccharide, or caprolactone moieties. For example, a lactidecan be grafted in between the ether units to provide degradation byhydrolysis.

Accordingly, the present invention provides a method of positioninginsect repellent structures on a multi-functional base polymer,preferably a polymer of the present invention provides insect protectionover a period of at least one day (i.e., at least about 24 hours), morepreferably at least three days (i.e., at least about 72 hours), morepreferably at least 1 week, and most preferably at least 1 month. Inmany cases, the stability of the bonding substrate determines theeffective duration. For example, the top layer of cells comprising skinnormally sloughs off with 50% of the skin area within three days.However, if the bonding substrate is a clothing article, the insectrepellent efficacy may last for months. The primary advantage of thepresent invention is that normally volatile compounds are covalentlybonded to a more durable substrate.

Additionally, there is a further benefit, in that many of the volatileinsect repellent compounds of the present invention are renderednon-volatile, that is they cannot be detected by smell. Essential oilsrepellent to insects tend to have strong odors which may be offensive.The present invention eliminates the formation of ambient odors, whichis also characteristic of their durability and longevity regardingefficacy.

In another embodiment, the polymeric backbone can have a star structure.For example, the triol can be further polymerized by three triols, oneattached to each are of the central triol to create a star configurationcomprising 6 arms, each terminated with a hydroxyl group. This starstructure then acts as the base polymer. The multifunctional aspect ofthe base polymer can serve to provide compounds that have a multiphasicfunctionality. While the ring stabilized form of the insect repellentstructures of the present invention have much extended residence timescompared to non-polymerized essential oils, these ring stabilizedstructures can localize free forms of the essential oils. That is, a fewprotein bonding molecules can serve as localizing centers for freeinsect repellent moieties.

Another embodiment provides insect repellent clothing articles and aclothing article comprising polymers, wherein the polymers andco-polymers possess a functional isocyanate group on one of the basepolymer arms. Such isocyanates are capable of bonding to other moleculeswith an amine or hydroxyl functionality. More specifically, the presentinvention relates to clothing articles and clothing article coatingshaving which include insect repellent, biocompatible, biodegradablepolymers and co-polymers.

Thus the present invention provides at least two was for enhancing aninsect repellent molecule biocompatibility. In one embodiment of thepresent invention the biocompatible, biodegradable, insect repellentpolymers and copolymers made in accordance with the teachings of thepresent invention are used to provide coatings for clothing articles.The coating may or may not include an additional bioactive agent on oneof the arms. For example, one arm of a polymer triol structure containsa UV absorptive group, another arm contains an isocyanate groups, and athird arm contains an insect repellent group.

In another embodiment of the present invention the entire clothingarticle is made using the biocompatible insect repellent polymers andcopolymers made in accordance with the teachings of the presentinvention.

Clothing articles made in accordance with the teachings of the presentinvention include, but are not limited to, screens, masks,undergarments, trousers, protective wear, gloves, facial covering,footwear, both functional and cosmetic.

The compounds and compositions of the invention are useful for treatingan animal, e.g., a mammal such as a human, for infestation with, forexample, a lice, a tick, or generally a parasite. The method comprisesadministering topically to the animal, e.g., human, an amount of acompound of the invention or composition thereof sufficient to treat theinfestation in the animal.

The following examples are meant to be illustrative, and not limiting.

Example 1

Synthesis of Polymer backbone: A poloxamer triol, such as dry (<300 ppmH2O) Multranol 3901 (Bayer, Morristown, N.J.) containing 1 mole ofhydroxyl groups, is combined with toluene diisocyanate containing 2moles of NCO groups in a glass reactor equipped with a stirrer, heatingjacket and temperature sensor. The reactor is purged with dry nitrogenand the mixture stirred. The reaction volume is heated to 40° C. andallowed to react until the exotherm has subsided. Then the temperatureof the reactor is increased in 5° C. increments, stopping after eachincrement to let the exotherm subside, until a temperature of 65° C. isreached. The reaction mixture is further reacted until 1 mole ofisocyanate group is consumed. This endpoint can be determined bymeasuring the % NCO.

Example 2

An insect repellent Polymer: The polymer backbone of Example 1 is placedin a reactor. The reactor is purged with dry nitrogen. The volume isstirred and an insect repellent molecule is delivered to the reactionvolume. The polymer will immediately begin to react with the introducedinsect repellent moiety. A solvent may be used in cases where thepolymer base or addition of insect repellent is too viscous.

For example, acetone can be used, and the solvent later removed byvacuum. Alternatively, an inert solvent such as propylene carbonate maybe used. The reaction is continued for approximately 12 hours at roomtemperature, in less time at elevated temperature. The reaction iscomplete when the residual NCO functionality is the original molarcontent.

Here, the protein bonding functionality can be adjusted to a particularapplication. For example, a protein bonding base of Example 1 comprising3 moles of NCO functionality, can be reacted with an insect repellentcomprising one hydroxyl group per molecule in a ratio of 1 mole ofExample 1 to 1 mole of insect repellent to yield polymers on averagethat have two protein bonding arms per molecule. On the other hand if 2moles of insect repellent are introduced into the reaction, then theresulting molecules will have on average 1 arm that is protein bonding.One can add 1 mole of one insect repellent moiety and another mole ofinsect repellent moiety to provide hybrid molecules.

Clearly, separate reactions can be performed where one insect repellentmolecule is formed, and another different insect repellent molecule isformed, and the two combined. Furthermore, molecules comprising two armsof insect repellent can be combined with molecules of Example 1 toincrease protein bonding.

Example 3

A Topical Bonding Insect Repellent: The insect repellent polymer ofExample 2 is mixed in an inert base with pleasing cosmetic attributes.The principal requirement for long shelf-life is that the base mixturepossess the lowest practical water content, typically less than 300 ppmH2O. For example, a mixture of butylene glycol, sodium lauroyllactylate, propylene glycol, poloxamer 407 and laureth-4 result in afoaming composition suitable for delivering the insect repellent polymerof Example 2 as a shower wash.

Effective concentrations of insect repellent polymer in topicalcompositions is generally between 10% and 50%.

Example 4

An Insect repellent Polymer with Tissue/Prosthetic BondingFunctionality: The polymer backbone of Example 1 is placed in a reactor.The reactor is purged with dry nitrogen. The volume is stirred andinsect repellent moiety is delivered to the reaction volume. The polymerbase will immediately begin to react with the introduced OH or NH groupsof the insect repellent. Viscosity will in most cases increase rapidly.A solvent may be used in cases where the polymer base is too viscous.For example, acetone can be used, and the solvent later removed byvacuum. Alternatively, an inert solvent such as propylene carbonate maybe used. The reaction is continued until approximately ⅔ of the NCOfunctionality is consumed. Clearly, any degree of tissue bondingfunctionality can be obtained by controlling the amount of NCOfunctionality that is consumed, typically greater than ⅓ of the NCOfunctionality and less than approximately ⅚ of the NCO functionality.

Example 5

A Clothing Article Coated with an Insect Repellent Polymer: A prostheticis coated with a solution of insect repellent polymer of Example 2. Theinsect repellent polymer may be diluted with a volatile solvent such astoluene or acetone. The coated clothing article is then allowed to curepartially in a humid environment. While the coating is still in a fluidstate, the coated clothing article is then transferred to a closed boxthat has been purged with dry nitrogen. The box is filled gaseous NO andthe coated prosthetic allowed to react with the NO until all isocyanatefunctionality is consumed.

Example 6

Test of an Insect Repellent Composition: A polymer backbone compositionof Example 1 is procured comprising 3 moles of NCO functionality (thispolymer is referred to as HAPI in FIG. 4). To this composition isreacted, as described in Example 2, 0.9 moles of OH comprising alcoholsof citronella essential oil extract, and 0.9 moles of OH comprisingalcohols of lemon eucalyptus essential oil extract, and 0.2 moles of OHcomprising alcohols of neem essential oil extract. This polymer wascompared to a polymer comprising picaridin, and to 100% DEET over a24-hour period of time. As seen in FIG. 4, the HAPI+cintronella/lemoneucalyptus composition had superior repelling activity over a longerperiod of time.

In summary, the materials and functions of the device of the inventioninclude the following: In one aspect of the invention, an insectrepellent polymer comprises: a) a biocompatible base polymer, b) atleast one aromatic ring, and c) an insect repellent group. Thebiocompatible base polymer is attached to the aromatic ring through aurethane or urea link at one position on the aromatic ring, and theinsect repellent group is attached at another site on the same aromaticring or on an additional aromatic ring. The biocompatible base polymeris multifunctional, and may be a poloxamer triol comprised ofpolypropylene and polyethylene segments. The insect repellent polymermay be made by reacting a multi-functional alcohol with a diisocyanateuntil all hydroxyl functionality is consumed to provide a macromulti-isocyanate, and by reacting said macro multi-isocyanate withinsect repellent until some fraction of isocyanate functionality isconsumed.

The insect repellent polymer may be used as a cosmetic base. It may alsocomprise an insect repellent polymer with bonding functionalitycomprising: a) a biocompatible base polymer, b) at least one aromaticring with pendant isocyanate functionality, and c) an insect repellentgroup, wherein the biocompatible base polymer is attached to thearomatic ring through a urethane or urea link at one position on thearomatic ring and the insect repellent group attached at another site onthe same or additional aromatic ring, and an isocyanate group at one ormore locations on one or more aromatic rings.

A clothing article may be coated with an insect repellent polymer. Thepolymer may include a UV absorptive group attached to isocyanate groupsthat are further reacted with a bioactive molecule.

A method of synthesizing an insect repellent polymer with bondingfunctionality may comprise the steps of: a) reacting a multi-functionalalcohol with a diisocyanate until all hydroxyl functionality is consumedto provide a macro multi-isocyanate, and b) said macro multi-isocyanatereacted with insect repellent OH or NH groups until a portion ofisocyanate functionality is consumed.

A method of coating a clothing article with an insect repellent polymermay comprise the steps of: a) coating the clothing article with thepolymer; b) partially polymerizing the polymer on the clothing article;and c) further reacting any remaining isocyanate groups with additionalinsect repellent moieties.

The nitric oxide releasing polymer of the invention is suitable fortreatment of a human, or for the coating of a clothing article, forexample by the reaction of an insect repellent polymer with a bioactivemolecule to coat a clothing article. It is also useful for coating aclothing article, directly or by coating the clothing article with abioactive molecule, or with an insect repellent polymer, and/or with acosmetic base.

Thus, although there have been described particular embodiments of thepresent invention of a new and useful TISSUE BONDING INSECT REPELLENT itis not intended that such references be construed as limitations uponthe scope of this invention except as set forth in the following claims.

What is claimed is:
 1. A topical insect repellent composition,comprising: i) a poloxamer triol bound to at least one insect-repellentmolecule via polymerization of a diisocyanate, and ii) a carriersuitable for application to the skin or hair; wherein the poloxamertriol is a polymerization product of a triol, the diisocyanate, and apoloxamer, such that the product is a polyol comprising 3 arms ofpoloxamer bonded to one triol; wherein the triol is trimethylolpropaneor glycerol; and wherein the insect-repellent molecule is a compoundextractable from a natural oil selected from the group consisting ofneem oil, citronella oil, and lemon eucalyptus oil.
 2. The compositionof claim 1, wherein the poloxamer triol is comprised of a blockcopolymer containing 10 to 60 carbon atoms per block.
 3. The compositionof claim 1, wherein the composition comprises an NCO weight fraction ofless than 20% of the total weight.
 4. The composition of claim 1,wherein the poloxamer triol is a multi-armed polymer, wherein at leastone arm comprises a terminal NCO group, and at least two other arms areeach bound to an insect-repellent molecule.
 5. The composition of claim4, wherein the multi-armed poloxamer triol is a three-armed polymer. 6.The composition of claim 1, wherein the poloxamer triol has a molecularweight between 1,000 and 20,000 Daltons.
 7. The composition of claim 4,wherein at least one arm of the poloxamer triol comprises at least oneterminal NCO group capable of bonding to human skin.
 8. The compositionof claim 7 wherein the poloxamer triol is capable of bonding to skin viaa covalent bond formed between the terminal NCO group and the skin. 9.The composition of claim 1, wherein the poloxamer triol is further boundto an ultraviolet-absorbing compound.
 10. The composition of claim 1wherein the carrier comprises a free insect repellent and a skinemollient.
 11. The composition of claim 10, wherein the free insectrepellent is selected from the group consisting of i) a synthetic insectrepellent, ii) a natural insect repellent and iii) combinations thereof.12. The composition of claim 11, wherein the synthetic insect repellentcomprises DEET.
 13. A topical insect-repellent composition, comprising:a compound comprising an insect-repellent molecule bound to a poloxamertriol, wherein the molecular weight of the compound is 500 Daltons orgreater, wherein the insect-repellent molecule is a compound extractablefrom a natural oil selected from the group consisting of neem oil,citronella oil, and lemon eucalyptus oil.
 14. The composition of claim13, wherein the insect-repellent molecule is p-menthane-3,8-diol. 15.The composition of claim 13, wherein the poloxamer triol furthercomprises at least one free isocyanate group.
 16. The composition ofclaim 13, wherein the insect-repellent molecule is picaridin.
 17. Thetopical insect repellant composition of claim 13, wherein the poloxamertriol is a polymerization product of: a triol selected fromtrimethylolpropane or glycerol, a diisocyanate, and a poloxamer.
 18. Thecomposition of claim 1, wherein the insect-repellent molecule is acompound extracted from a natural oil selected from the group consistingof neem oil, citronella oil, and lemon eucalyptus oil.
 19. Thecomposition of claim 13, wherein the insect-repellent molecule is acompound extracted from a natural oil selected from the group consistingof neem oil, citronella oil, and lemon eucalyptus oil.